Friday, 31 January 2020

Mammoth Biosciences aims to be Illumina for the gene editing generation

In 1998, the startup company Illumina launched a revolution in the life sciences industry by developing technology to slash the costs of identifying and mapping genetic material.

Now, a little over 20 years later, Mammoth Biosciences is hoping to do the same thing for gene editing tools.

The company, co-founded by Jennifer Doudna, who did some of the pioneering work to discover the gene editing enzyme known as CRISPR, has just raised $45 million as it looks to bring to market products that can be used not only for disease detection, but are more precise editing tools for genetic material.

Rather than get bogged down in the patent dispute that raged over the provenance and ownership of applications for the original CRISPR enzyme — the Cas9 discovered by Doudna and developed for clinical applications at the Broad Institute — Mammoth has joined a number of startups in identifying new enzymes with a broader array of properties.

“From the very beginning of the company we’ve only worked with novel new enzymes to create these diagnostic products and the new novel diagnostic and editing,” says Trevor Martin, Mammoth Biosciences co-founder and chief executive.

Chiefly, the company is touting its Cas14 enzyme, which the company says opens up new possibilities for programmable biology thanks to its small size, diverse targeting ability and high fidelity — meaning that there are no unforeseen side effects to edits made using the enzyme (something that has arisen with Cas9 applications).

“There’s not one protein that’s going to be the best at everything,” says Martin. “For any particular product that you’re building, at Mammoth, we have the broadest toolbox.”

The Cas14 enzyme can be used to make gene edits in-vivo, meaning in live organisms, instead of ex-vivo, or outside of an organism. The in-vivo use-case could accelerate the time it takes to conduct experiments or develop treatments.

“Twenty years from now, when the umpteenth drug gets approved using Crispr and some nuclease named Cas132013, people are going to look back on this patent battle and think, ‘what a godawful waste of money,’ ” Jacob Sherkow a patent law scholar at New York Law School told Wired back in 2018.

Already, Horizon Discovery, a Cambridge, U.K.-based gene editing technology developer, is using the new tools developed by Mammoth Bioscience to create new CRISPR tools for Chinese Hamster Ovary cell line editing.

That partnership is an example of how Mammoth is thinking about the commercialization of the new Cas14 enzyme line and its role in biological engineering.

“You will need a full toolbox of CRISPR proteins,” says Martin. “That will allow you to interact with biology in the same way that we interact with software and computers. “From first principles, companies will programmatically modify biology to cure a disease or decrease risk for a disease. That’s going to be really kind of a turning point.”

To achieve its vision, Mammoth has managed to nab top talent from the life sciences industry, including Peter Nell, a co-founder of Casebia (a joint venture between Bayer and CRISPR Therapeutics), who came on board as chief business officer, and Ted Tisch, a former executive at Synthego and Bio-Rad, who joined the company as chief operating officer.

The company also nabbed $45 million of funding, including investment firms Mayfield, NFX, Verily (the Alphabet subsidiary) and Brook Byers, which was led by Decheng Capital — bringing the company to more than $70 million in funding.

“There are a dozen or so products that are in clinical development with CRISPR,” says Ursheet Parikh, a partner with Mayfield. “Maybe that number would go up by five or 10 without Mammoth, but it will go up by one or two orders of magnitude with Mammoth.”

To Parikh, Mammoth is the best positioned of the CRISPR development tools, because the company is building a whole platform that customers can license and use to develop products using gene editing.

The thinking, according to Parikh, is as follows, “if this technology can power lots of applications, let’s basically ensure that lots of these applications can come to market and as that happens I get my app store cut.”

“It’s an Illumina-like business,” Parikh says. “Just as anybody who is innovating with genomics needs an Illumina sequencer because they want to be able to do the sequencing… if someone wants to do editing… This gives them the access to do the right sequencing.”



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